Can we cure indolent lymphomas?

The current consensus is that indolent lymphomas are incurable disorders. There are some indications that these malignancies are potentially curable. Indeed, not all indolent lymphomas are currently incurable. For example, patients with Ann Arbor stage I-II indolent lymphomas can experience long-term disease-free survival and probable cure. Also, from the available literature data, it seems that the achievement of a molecular complete remission is a desirable objective. Patients who achieve a persistently negative PCR state seldom relapse, whereas the opposite is true for persistently positive cases. In view of its excellent correlation with disease-free survival when examined serially in multiple blood or marrow samples, the PCR technique has the potential of providing a tumor marker that can be used as an early end point for clinical trials. By serving as an early surrogate end point, PCR could play an important role in expediting the development of new treatment strategies. Whether IFN is capable of increasing the molecular complete remission rate as measured by PCR is not known. However, it is clear that from the clinical standpoint, IFN has been able to increase 2-fold the length of remission in patients with advanced indolent lymphomas. In at least two studies, this has been associated with prolongation of survival. More intensive regimens such as alternating triple therapy, when used in combination with IFN, seem to have improved the quality of remissions as judged by the PCR assay. Finally, the site where the bcl-2 breakpoint occurs seems to have clinical significance. Those follicular lymphomas with germ-line bcl-2, in our experience, have behaved more aggressively than the others, and their failure-free survival seems different from the usual indolent lymphomas and more closely resembles the large cell lymphomas. Although the biological significance of this observation is not yet understood, this group might actually constitute a prognostically different subset with a more aggressive and perhaps more curable lymphoma. Whether the plateau observed in their failure-free survival curve will be maintained with more follow-up and whether they might be a curable subset remain to be determined.